NM_004006.3(DMD):c.4934_4937del (p.Lys1645fs) AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000461657.5

Allele description [Variation Report for NM_004006.3(DMD):c.4934_4937del (p.Lys1645fs)]

NM_004006.3(DMD):c.4934_4937del (p.Lys1645fs)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.4934_4937del (p.Lys1645fs)

HGVS:

NC_000023.10:g.32383225_32383228del
NC_000023.11:g.32365110_32365113del
NG_012232.1:g.979499_979502del
NM_000109.4:c.4910_4913del
NM_004006.3:c.4934_4937delMANE SELECT
NM_004009.3:c.4922_4925del
NM_004010.3:c.4565_4568del
NM_004011.4:c.911_914del
NM_004012.4:c.902_905del
NP_000100.3:p.Lys1637fs
NP_003997.2:p.Lys1645fs
NP_004000.1:p.Lys1641fs
NP_004001.1:p.Lys1522fs
NP_004002.3:p.Lys304fs
NP_004003.2:p.Lys301fs
LRG_199:g.979499_979502del
NC_000023.10:g.32383225_32383228del
NC_000023.10:g.32383225_32383228delTCCT
NC_000023.10:g.32383227_32383230del
NM_004006.2:c.4934_4937delAGGA

Protein change:

K1522fs

Links:

dbSNP: rs1060502632

NCBI 1000 Genomes Browser:

rs1060502632

Molecular consequence:

NM_000109.4:c.4910_4913del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004006.3:c.4934_4937del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004009.3:c.4922_4925del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004010.3:c.4565_4568del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004011.4:c.911_914del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004012.4:c.902_905del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Duchenne muscular dystrophy (DMD)
Synonyms:: Muscular dystrophy, pseudohypertrophic progressive, Duchenne type
Identifiers:: MONDO: MONDO:0010679; MedGen: C0013264; Orphanet: 98896; OMIM: 310200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550281	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16770791, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550281

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule.

Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT.

Muscle Nerve. 2006 Aug;34(2):135-44. Review.

PubMed [citation]

PMID:: 16770791

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550281.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in DMD are known to be pathogenic (PMID: 16770791). This sequence change deletes 4 nucleotides from exon 35 of the DMD mRNA (c.4934_4937delAGGA), causing a frameshift at codon 1645. This creates a premature translational stop signal (p.Lys1645Argfs*11) and is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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